Significant Reduction In Immobility Time Research Articles

Evaluation of Antidepressant Activity of Leaf Extract of Curculigo orchioides Gaertn in mice

Depression is mood disturbances that causes a continuous feeling of unhappiness, changes in behavior, unable to concentrate and loss of interest. Chronic exposure to stressful events plays very important role in the etiology of depression. Curculigoorchioides is a medicinally important plant that is used widely in ayurvedic system of medicine and Chinese traditional systems. The present study was undertaken to evaluate the antidepressant activity of the Curculigoorchioides leaf extract in mice exposed to acute stress in different behavioural models like forced swimming test, tail suspension test, 5-Hydroxy Tryptamine (5-HTP) induced head twitches. The effect of the extract on brain lipid peroxidation was also assessed by invitro estimation of malondialdehyde levels. After the oral administration of leaf extract of Curculigoorchioides at the dose of 100, 200 and 400mg/kg to the mice antidepressant activity was compared with the standarddrug imipramine (10mg/kg). The Curculigoorchioides leaf extract showed significant reduction in immobility time and increased number of 5-Hydroxy Tryptamine induced head twitchesin dose-dependent manner. Significant antidepressant activity of Curculigoorchioides leaf extract was observed at the dose of 100mg/kg which was evident by the reduced duration of immobility in forced swimming and tail suspension test. Extract treatedgroups showed reduced brain lipid peroxidation indicated by decrease in malondialdehyde content. Hence Curculigoorchioidesleaf extract possess antidepressant activity.

Preclinical Validation of Electrodes for Single Anodal Transcranial Direct Current Stimulation on Rat Model With Chronic Stress-Induced Depression

Transcranial direct current stimulation (tDCS) is an effective and safe non-invasive brain stimulation (NIBS) procedures to modulate neuronal excitability. The present preclinical study was carried out to validate the impact of the innovative high definition fabricated spiking Au/AgCI electrodes via non-invasive tDCS procedure on rat model with depression-like behaviour. In present study, chronic stress induced depression like behaviour rat model was developed over a period of 14-days. Further, the after-effects of NIBS procedures were investigated by providing a tDCS dose (2.00mA × 5.00minutes) by placing the electrodes on the interested region of the rat brain. The current study was performed in healthy rats, control rats with depression-like behaviour, and tDCS treated rats, which were used to examine the differential after-effects of tDCS dose. After single tDCS dose, a significant increase in average band power of electroencephalogram (EEG) has been observed (F(2, 15) = 8.376; P = 0.0036) alongside a significant increase in the glutamate level of hippocampus (F(2, 15) = 8.919; P = 0.0028), a significant reduction in immobility time (F(2, 15) = 7.552; P = 0.0054), and a significant increase in the percentage sucrose intake has been observed (F(2,15) = 5.941; P = 0.0126). Additionally, immunohistochemistry (IHC) showed a significant increase in theIba1 protein expression in microglia cell in the both cortex and hippocampus region (P < 0.05). Hence, the fabricated electrodes can deliver a tDCS dose that can penetrate up to the cortex and hippocampus regions from the surface of brain non-invasively within tolerable and safety limits.

Gut microbiota from sigma-1 receptor knockout mice induces depression-like behaviors and modulates the cAMP/CREB/BDNF signaling pathway.

Depression is a common mental disorder that affects approximately 350 million people worldwide. Much remains unknown about the molecular mechanisms underlying this complex disorder. Sigma-1 receptor (Sig-1R) is expressed at high levels in the central nervous system. Increasing evidence has demonstrated a close association between the Sig-1R and depression. Recently, research has suggested that the gut microbiota may play a crucial role in the development of depression. Male Sig-1R knockout (Sig-1R KO) and wild-type (WT) mice were used for this study. All transgenic mice were of a pure C57BL/6J background. Mice received a daily gavage of vancomycin (100 mg/kg), neomycin sulfate (200 mg/kg), metronidazole (200 mg/kg), and ampicillin (200 mg/kg) for one week to deplete gut microbiota. Fecal microbiota transplantation (FMT) was conducted to assess the effects of gut microbiota. Depression-like behaviors was evaluated by tail suspension test (TST), forced swimming test (FST) and sucrose preference test (SPT). Gut microbiota was analyzed by 16s rRNA and hippocampal transcriptome changes were assessed by RNA-seq. We found that Sig-1R knockout induced depression-like behaviors in mice, including a significant reduction in immobility time and an increase in latency to immobility in the FST and TST, which was reversed upon clearance of gut microbiota with antibiotic treatment. Sig-1R knockout significantly altered the composition of the gut microbiota. At the genus level, the abundance of Alistipes, Alloprevotella, and Lleibacterium decreased significantly. Gut microbiota dysfunction and depression-like phenotypes in Sig-1R knockout mice could be reproduced through FMT experiments. Additionally, hippocampal RNA sequencing identified multiple KEGG pathways that are associated with depression. We also discovered that the cAMP/CREB/BDNF signaling pathway is inhibited in the Sig-1R KO group along with lower expression of neurotrophic factors including CTNF, TGF-α and NGF. Fecal bacteria transplantation from Sig-1R KO mice also inhibited cAMP/CREB/BDNF signaling pathway. In our study, we found that the gut-brain axis may be a potential mechanism through which Sig-1R regulates depression-like behaviors. Our study provides new insights into the mechanisms by which Sig-1R regulates depression and further supports the concept of the gut-brain axis.

Once-Daily Subcutaneous Irisin Administration Mitigates Depression- and Anxiety-like Behavior in Young Mice

Major depression is one of the most common psychiatric disorders worldwide, usually associated with anxiety. The multi-etiological nature of depression has increased the search for new antidepressant molecules, including irisin, for which, in a previous study, we tested its effect in young mice when administered intraperitoneally in a long-term intermittent manner. Here, we evaluated the effect of subcutaneous short-term irisin administration (100 µg/Kg/day/5 days) in male and female mice subjected to behavioral paradigms: Tail Suspension Test (TST), Forced Swim Test (FST), Elevated Plus Maze (EPM), and Y Maze (YM). Moreover, a qRT-PCR assay was performed to analyze the impact of irisin treatment on Pgc-1α/FNDC5 expression in the brain. A significant reduction in immobility time in TST and FST was observed in irisin-treated mice. Furthermore, irisin treatment significantly increased the number of entries and time spent in open arms, demonstrating its anxiolytic effect. Memory-enhancing effects were not reported in YM. Interestingly, no gender differences were observed in all behavioral tests. Overall, these results suggest that short-term subcutaneous irisin administration can exert an antidepressant and anxiolytic role, probably due to the activation of the Pgc-1α/FNDC5 system in the brain. Further investigation could lead to the identification of irisin as a new agent for the treatment of psychiatric disorders.

Lithium augmentation of ketamine increases insulin signaling and antidepressant-like active stress coping in a rodent model of treatment-resistant depression

Lithium, a mood stabilizer and common adjunctive treatment for refractory depression, shares overlapping mechanisms of action with ketamine and enhances the duration of ketamine’s antidepressant actions in rodent models at sub-therapeutic doses. Yet, in a recent clinical trial, lithium co-treatment with ketamine failed to improve antidepressant outcomes in subjects previously shown to respond to ketamine alone. The potential for lithium augmentation to improve antidepressant outcomes in ketamine nonresponders, however, has not been explored. The current study examined the behavioral, molecular and metabolic actions of lithium and ketamine co-treatment in a rodent model of antidepressant resistance. Male Wistar rats were administered adrenocorticotropic hormone (ACTH; 100 µg/day, i.p. over 14 days) and subsequently treated with ketamine (10 mg/kg; 2 days; n = 12), lithium (37 mg/kg; 2 days; n = 12), ketamine + lithium (10 mg/kg + 37 mg/kg; 2 days; n = 12), or vehicle saline (0.9%; n = 12). Rats were subjected to open field (6 min) and forced swim tests (6 min). Peripheral blood and brain prefrontal cortical (PFC) tissue was collected one hour following stress exposure. Western blotting was used to determine the effects of treatment on extracellular signal-regulated kinase (ERK); mammalian target of rapamycin (mTOR), phospho kinase B (Akt), and glycogen synthase kinase-3ß (GSK3ß) protein levels in the infralimbic (IL) and prelimbic (PL) subregions of the PFC. Prefrontal oxygen consumption rate (OCR) and extracellular acidification rates (ECAR) were also determined in anterior PFC tissue at rest and following stimulation with brain-derived neurotrophic factor (BDNF) and tumor necrosis factor α (TNFα). Blood plasma levels of mTOR and insulin were determined using enzyme-linked immunosorbent assays (ELISAs). Overall, rats receiving ketamine+lithium displayed a robust antidepressant response to the combined treatment as demonstrated through significant reductions in immobility time (p < 0.05) and latency to immobility (p < 0.01). These animals also had higher expression of plasma mTOR (p < 0.01) and insulin (p < 0.001). Tissue bioenergetics analyses revealed that combined ketamine+lithium treatment did not significantly alter the respiratory response to BDNF or TNFα. Animals receiving both ketamine and lithium had significantly higher phosphorylation (p)-to-total expression ratios of mTOR (p < 0.001) and Akt (p < 0.01), and lower ERK in the IL compared to control animals. In contrast, pmTOR/mTOR levels were reduced in the PL of ketamine+lithium treated animals, while pERK/ERK expression levels were elevated. Taken together, these data demonstrate that lithium augmentation of ketamine in antidepressant nonresponsive animals improves antidepressant-like behavioral responses under stress, together with peripheral insulin efflux and region-specific PFC insulin signaling.

Evaluation of antidepressant activity of ethanolic extract of Mimosa pudica in swiss albino mice

Depression is a widely prevalent form of mental illnesses worldwide. It is commonly associated with sad mood, loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, and low energy. has many medicinal properties, and are used in traditional medicine in the treatment of various medical conditions. This study was conducted to better understand the antidepressant activity of Mimosa pudica. To evaluate the potential antidepressant activity of Ethanolic Extract of (EEMP) leaves on depression in Swiss Albino mice. Swiss albino mice of either sex weighing 20-30g were used. Sixty mice were divided into two arms. Each arm was further divided into five groups (n=6). Drugs were given orally once daily, for ten days. Group 1 was the Control group and received saline. Group 2 received standard drug – Imipramine (15mg/kg). Group 3 received EEMP (100mg/kg). Group 4 received EEMP (200mg/kg). Group 5 received EEMP (400mg/kg). Antidepressant potential of EEMP was evaluated by submitting the mice to Forced Swim Test (FST) and Tail Suspension Test (TST) on the first and tenth day. The study showed significant reduction in immobility time in both Forced Swim Test and Tail Suspension Test in the EEMP group when compared with the control group. The study suggests that Ethanolic Extract of has anti-depressant activity and can be considered for use in therapy of depression after further testing.

COMPARATIVE STUDY OF ANTIDEPRESSANT-LIKE EFFECT OF THE LEAVES OF SAPINDUS EMARGINATUS AND ACORUS CALAMUS IN EXPERIMENTAL ANIMAL MODELS

Objective: Depression is an affective disorder characterized by a change in mood, lack of confidence, lack of interest in surroundings and many natural products that have been tried to treat the disease. The study was aimed to evaluate and compare the antidepressant activity of methanol leave extract of SapindusemarginatusVahl. (MESE) and Acoruscalamus Linn. (MEAC) in experimental models in albino mice.&#x0D; Methods: Methanol Extracts of the plants were prepared by soxhlet extraction method. Forced swimming test (FST) and Tail suspension test (TST) models were chosen to evaluate antidepressant activity.Albino mice were selected and divided into six groups of six animals for each experimental model. Group I received 1% gum acacia in distilled water (DW) at a dose of 1 ml/100 g orally. Group II received sertraline-10 mg/kg orally. Group III and IV were administered 200 and 400 mg/kg of MESE respectively. Group V and VI were treated with 200 and 400 mg/kg of MEAC, respectively.&#x0D; Results: Methanol extracts of Sapindusemarginatus and Acoruscalamus at the two different doses of 200 and 400 mg/kg demonstrated a significant decrease in immobility time when compared with the control in both animal models. The extracts at the higher dose of 400 mg/kg revealed a significant reduction in immobility time compared to 200 mg/kg of the same extract.&#x0D; Conclusion: The results suggest that the methanol extracts of SapindusemarginatusVahl. andAcoruscalamus Linn. possessthe anticonvulsant activityand justify their use in folk medicine.

Antidepressant Activity of Nardostachys jatamansi Extract in Animal Models of Depression

Background: Depression refers to a wide range of mental health problems characterized by the loss of interest in routine activities, low mood and a range of associated emotional, cognitive, physical and behavioral symptoms. It is one of the major causes of mortality as tendency of suicidal attacks are exhibited in these patients. The diagnosis of depressive patients is very complicated in many cases and they do not respond to rational clinical prescription. In traditional medicine, Nardostachys jatamansi has been used as stimulant, antispasmodic, laxative and antiepileptic in ayurvedic and unani systems of medicine. The objective of our study was to evaluate and compare the antidepressant activity of N. jatamansi extract with fluoxetine in animal models of depression.&#x0D; Methodology: It was a preclinical experimental study in which Total 100 BALB/c mice divide into 14 groups i.e. Group 1 &amp; 2 control 0.9% NaCl i.p for forced swimming test (FST) and tail suspension test (TST) respectively, Group 3 &amp; 4 Fluoxetine 0.5 mg/kg i.p for FST and TST respectively, Group 5, 6 &amp; 7 of N. jatamansi 125, 250 and 500 mg/kg respectively for FST, Group 8, 9 &amp; 10 N. jatamansi 125, 250 and 500 mg/kg respectively for TST, Group 11 N. jatamansi (most effective dose) for Locomotor Test, Group 12 NaCl 0.9% for Yohimbine Potentiation Test (YPT), Group 13 Fluoxetine 0.5 mg/kg for YPT and Group 14 Received extract of N. jatamansi (most effective dose) for YPT. Antidepressant activity of N. jatamansi extract at different doses after induction of depression via FST and TST was recorded. Moreover the antidepressant effect was confirmed by locomotor test. YPT was also applied to comment on possible underlying mechanism.&#x0D; Results: In our study 250 mg/kg and 500 mg/kg doses of N. jatamansi showed significant reduction in immobility time when compared to controls and 500 mg/kg showed significant reduction as compared to group given fluoxetine in FST model. All the groups in TST model showed significant reduction in immobility time when compared to controls and fluoxetine given group. N. jatamansi at the dose of 500 mg/kg was found to be most effective in both the models. No significant change in locomotor activity was found in locomotor test. The percentage mortality of 50% was observed in N. jatamansi group using yohimbine potentiation test.&#x0D; Conclusion: In our study Nardostachys jatamansi showed significant reduction in immobility time when compared to controls and fluoxetine.

Pharmacological insights and prediction of lead bioactive isolates of Dita bark through experimental and computer-aided mechanism

Dita bark (Alstonia scholaris (L.) R. Br.) is an ethnomedicine used for the management of various ailments. This study aimed to investigate the biological properties of methanol extract of A. scholaris bark (MEAS), through in vivo, in vitro and in silico approaches alongside its phytochemical profiling. Identification and nature of the bioactive secondary metabolites were studied by the established qualitative tests and GC–MS analysis. The antidepressant activity was determined by forced swimming test (FST) and tail suspension test (TST) in mice. The anti-inflammatory and thrombolytic effect was evaluated using inhibition of protein denaturation technique and clot lysis technique, respectively. Besides, computational studies of the isolated compounds and ADME/T analysis were performed by Schrödinger-Maestro (v11.1) software, and PASS prediction was conducted through PASS online tools. The GC–MS analysis revealed the presence of several secondary metabolites in MEAS. Treatment with MEAS revealed a significant reduction of immobility time in a dose-dependent manner in FST and TST. Besides, MEAS showed substantial anti-inflammatory effects at the higher dose (400 μg/mL) as well as revealed notable clot lysis effect as compared to control. In the case of computer-aided investigation, all compounds meet the condition of Lipinski’s rule of five. PASS study also predicted for all compounds, and among these safe compound furazan-3-amine showed the most spontaneous binding energy for both antidepressant and thrombolytic activities, as well as 5-dimethylamino-6 azauracil, found promising for anti-inflammatory activity. Taken together, the investigation concludes that MEAS can be a potent source of antidepressant, anti-inflammatory, and thrombolytic agents.

P.125 Samidorphan, an opioid receptor antagonist, mitigates olanzapine-induced metabolic dysfunction in female rats

We have earlier reported antidepressant-like effect of Cnestis ferruginea and its bioflavonoid constituent, amentoflavone in behavioural paradigms but its effects on neurochemical and neuroendocrine systems are yet to be elucidated. This study sought to investigate the effect of subchronic treatment of C. ferruginea (CF) on monoamines system, hypothalamo-pituitary adrenal axis and nitrosative/oxidative stresses. Male albino rats (150–200 g) randomly divided into seven groups; Group I: vehicle treated (0.2%v/v Tween 80 in normal saline (10 ml/kg; p.o.; unstressed), Group II: vehicle treated + restraint stress, Group III: imipramine (20 mg/kg; p.o.), Group IV–VI: CF (12.5, 50, or 100 mg/kg; p.o., respectively), Group VII: CF 6.25 + imipramine 5 mg/kg. One hour post-treatment, animals were subjected to 20 min restraint stress and 6 min, forced swim test (FST) for a period of 14 days. CF (12.5, 50 and 100 mg/kg) produced significant reduction in immobility time and an increase in climbing behaviour. CF attenuated repeated restraint stress × FST-induced serum corticosterone [F(6,28) = 5.45,P < 0.01]. Exposure of rats to FST + restraint stress paradigms produced significant (P < 0.05) increase in malondialdehyde and nitrite level, also reduced the glutathione level and superoxide dismutase activity which was reversed by subchronic treatment of rats with CF. Restraint stress × FST significantly decreased NA, DA and 5-HT concentrations, with increased DA and 5-HT turnover ratios in discrete brain regions which was ameliorated by CF or imipramine subchronic treatment. These results suggest that the antidepressant-like effect of C. ferruginea involved enhancement of monoamines and antioxidant as well as normalization of neuroendocrine systems.

Formulation of polymeric nanoparticles of antidepressant drug for intranasal delivery.

Aim: The manuscript describes the performance of nanoparticles loaded with antidepressant drug for nose-to-brain drug delivery. Materials & methods: Poly-lactic-co-glycolic acid-loaded nanoparticles of agomelatine were prepared by nanoprecipitation method using poloxamer 407 as stabilizer. The process parameters were optimized using factorial design. Results: The drug-loaded nanoparticles having low particle size (<200nm) with narrow size distribution and required zeta potential (-22.7mV) to avoid aggregation showed sustained release profile and were found to have higher permeability as observed from ex vivo studies when compared with plain drug suspension. Histopathology test showed that the optimized formulation was free from nasal toxicity on the goat nasal mucosa. Pharmacodynamic study showed significant reduction in immobility time in rats treated with the formulation which indicated antidepressant activity of the formulation. Conclusion: The prepared agomelatin-loaded poly-lactic-co-glycolic acid nanoparticles showed prominent antidepressant activity by nose-to-brain delivery as observed from various studies.

Samidorphan mitigates olanzapine-induced weight gain and metabolic dysfunction in rats and nonhuman primates

We have earlier reported antidepressant-like effect of Cnestis ferruginea and its bioflavonoid constituent, amentoflavone in behavioural paradigms but its effects on neurochemical and neuroendocrine systems are yet to be elucidated. This study sought to investigate the effect of subchronic treatment of C. ferruginea (CF) on monoamines system, hypothalamo-pituitary adrenal axis and nitrosative/oxidative stresses. Male albino rats (150–200 g) randomly divided into seven groups; Group I: vehicle treated (0.2%v/v Tween 80 in normal saline (10 ml/kg; p.o.; unstressed), Group II: vehicle treated + restraint stress, Group III: imipramine (20 mg/kg; p.o.), Group IV–VI: CF (12.5, 50, or 100 mg/kg; p.o., respectively), Group VII: CF 6.25 + imipramine 5 mg/kg. One hour post-treatment, animals were subjected to 20 min restraint stress and 6 min, forced swim test (FST) for a period of 14 days. CF (12.5, 50 and 100 mg/kg) produced significant reduction in immobility time and an increase in climbing behaviour. CF attenuated repeated restraint stress × FST-induced serum corticosterone [F(6,28) = 5.45,P < 0.01]. Exposure of rats to FST + restraint stress paradigms produced significant (P < 0.05) increase in malondialdehyde and nitrite level, also reduced the glutathione level and superoxide dismutase activity which was reversed by subchronic treatment of rats with CF. Restraint stress × FST significantly decreased NA, DA and 5-HT concentrations, with increased DA and 5-HT turnover ratios in discrete brain regions which was ameliorated by CF or imipramine subchronic treatment. These results suggest that the antidepressant-like effect of C. ferruginea involved enhancement of monoamines and antioxidant as well as normalization of neuroendocrine systems.

Salvia officinalis induces antidepressant-like effect, anxiolytic activity and learning improvement in hippocampal lesioned and intact adult rats.

The anxiolytic and antidepressant like effects of Salvia officinalis extract (50, 100 and 200 mg/kg) were evaluated using marble burying, forced swimming and open-field tests in intact and hippocampal lesioned rats. Additionally, S. officinalis was evaluated on rat's memory using conditioned learning test. and we screened the methanolic extract for anti-oxidant activity, phytochemical and high performance liquid chromatography analyses. The administration of sage extract showed a significant reduction of immobility time in lesioned and intact animals during the forced swim test and anxiolytic effect in marble burying test. In the case of conditioned learning paradigm, memory enhancement was observed in sage treated group which indicates a cognition improvement. These activities seem to be related to the anti-oxidant capacity and the phytochemicals (phenolic, flavonoid, and tannin) detected into the extract of S. officinalis. The findings show that the methanolic extract of sage possess antidepressant-like effect, anxiolytic activity and also may contain bioactive compounds that stimulate learning in rat.

Synthesis and biological evaluation of magnolol derivatives as melatonergic receptor agonists with potential use in depression

Depression is associated with high mortality and morbidity rates worldwide. By our random screening, it was first revealed that 23 magnolol derivatives were synthesized followed by in vitro and in vivo evaluation of their antidepressive potential. Compound 7c was found to be the most promising compound, with EC50 values of 396.5 and 383.0 μM agitating on MT1 and MT2 receptors, respectively. Additionally, we carried out in vivo experiments to confirm the efficacy and safety of compound 7c; the compound was found to be orally bioavailable and highly effective, leading to a significant reduction of immobility time in a mouse model of depression (forced swimming test and tail suspension test); the acting mechanism was explored by determining its effect on the levels of monoamine neurotransmitters and their metabolites in different mice brain regions; the acute toxicity study showed that the 50% lethal dose (LD50) of 7c was higher than 2000 mg/kg, p. o. A total of 25 metabolites of 7c were identified, including 5 metabolites in phase I and 20 metabolites in phase II. Altogether, these results indicate that magnolol derivative 7c is a promising lead compound for the development of a new chemical class of antidepressant drugs.

Antidepressant Activity of Methanolic Extract of Vitis vinifera

The present study was determined to evaluate the effect of methnolic extract of Vitis vinifera (MEVV) as well as its interaction with conventional antidepressant drug using tail suspension test (TST) and forced swim test (FST) and to evaluate the possible mechanisms involved in its actions. The extract was found to reduce the explorative tendencies of the rats in the tail suspension test and forced swim test the extract caused a significant reduction in immobility time and increased swimming time. The leaf of the plant were collected and authenticated. The methnolic extract of Vitis vinifera (MEVV) showed the significant antidepressant activity comparable to the standard drug. The oral administration of methnolic extract of Vitis vinifera (MEVV) at 100, 200 and 400 mg/kg respectively as compared to the control treated group showed an antidepressant activity comparable to that of standard drug. The antidepressant effects of methnolic extract of Vitis vinifera (MEVV) having a particular quality to be mainly associated with the activation of dopamineergic system and possess potential antidepressant activities.

STUDY OF THE ANTIDEPRESSANT ACTIVITY OF FOLIC ACID AND VITAMIN-D ON RESERPINE INDUCED DEPRESSION IN MICE.

Objective: Low levels of folic acid and deficiency of Vitamin D have been found to be associated with poor mood and depression. This study was designed to investigate whether these vitamins show antidepressant activity in models of depression in mice.Methods: Reserpine was used to induce depression in the study groups. Low and high doses of folic acid and Vitamin D as well as combinations of these vitamins in low and high doses were administered after induction of depression. The test animals were then tested on forced swim test, tail suspension test, and open field test models for evaluation of the antidepressant activity.Results: After 2 weeks of drug treatment, all the treated groups showed a significant reduction in immobility time in both the test models (p&lt;0.05). High dose folic acid showed consistently greater antidepressant property in all the test models throughout the study period. High dose Vitamin D (p&lt;0.05) also showed good antidepressant activity after 2 weeks, the delayed antidepressant effect of which might be attributable to the molecular mechanism of action of Vitamin D.Conclusion: Our study demonstrates that both folic acid and Vitamin D have antidepressant activity. The antidepressant activity of high dose folic acid (50 mg/kg) in reserpine-induced depression in mice at the end of 2 weeks was more pronounced in our study. Studies with longer duration of treatment are warranted to further evaluate their antidepressant effect.

Protective Effects of Morin Hydrate on Acute Stress-Induced Behavioral and Biochemical Alterations in Mice.

Introduction:As stress affects the brain both physiologically and chemically, researchers try to find novel anti-stress compounds with beneficial therapeutic effects. In this regard, the effect of stress and its modulation by Morin hydrate was studied using different acute models in mice.Methods:The models employed were anoxic tolerance, swimming endurance, and acute restraint test. Morin hydrate or the vehicle was administered 30 minutes prior to each stress exposure while in the acute restraint test; the animals were pretreated for 7 days with Morin hydrate, vehicle, imipramine, or diazepam before stress exposure. The measured parameters were the onset of convulsion and immobility time in the anoxic tolerance and swimming endurance test, respectively, while in the acute restraint test, the animals were assessed for stress-induced anxiety using the elevated plus maze and depression using the forced swim test. Thereafter blood was withdrawn from the retro-orbital plexus and plasma separated, the brain was also isolated, homogenized, centrifuged, and the supernatant was obtained for biochemical estimation.Results:Morin hydrate (5, 10, 20 mg/kg) produced a significant reduction in immobility time in the swimming endurance test, while significantly increased the anoxic stress tolerance time. Acute restraint stress caused a significant decrease in reduced glutathione levels (which was reversed by Morin hydrate) and increased the level of malondialdehyde, a thiobarbituric acid reactive substance which is an index of oxidative stress and nitrite. These effects were attenuated by Morin hydrate. Also, pretreatment with Morin hydrate attenuates acute restraint stress-associated anxiety and depression, reversed the hyperglycemia evoked by the stressful exposure and normalized serum cholesterol levels.Conclusion:These findings suggest that Morin hydrate exhibits anti-stress effects and may be useful in the relief of stress.

Rapid antidepressant effect of ketamine correlates with astroglial plasticity in the hippocampus.

Astroglia contribute to the pathophysiology of major depression and antidepressant drugs act by modulating synaptic plasticity; therefore, the present study investigated whether the fast antidepressant action of ketamine is reflected in a rapid alteration of the astrocytes' morphology in a genetic animal model of depression. S-Ketamine (15mg·kg-1 ) or saline was administered as a single injection to Flinders Line (FSL/ FRL) rats. Twenty-four hours after the treatment, perfusion fixation was carried out and the morphology of glial fibrillary acid protein (GFAP)-positive astrocytes in the CA1 stratum radiatum (CA1.SR) and the molecular layer of the dentate gyrus (GCL) of the hippocampus was investigated by applying stereological techniques and analysis with Imaris software. The depressive-like behaviour of animals was also evaluated using forced swim test. FSL rats treated with ketamine exhibited a significant reduction in immobility time in comparison with the FSL-vehicle group. The volumes of the hippocampal CA1.SR and GCL regions were significantly increased 1day after ketamine treatment in the FSL rats. The size of astrocytes in the ketamine-treated FSL rats was larger than those in the FSL-vehicle group. Additionally, the number and length of the astrocytic processes in the CA1.SR region were significantly increased 1day following ketamine treatment. Our results support the hypothesis that astroglial atrophy contributes to the pathophysiology of depression and a morphological modification of astrocytes could be one mechanism by which ketamine rapidly improves depressive behaviour.

Antidepressant Activity of Ethanol Leaf Extract of Annona muricata L., in Sprague-Dawley Rats

Background: Annona muricata L. is a plant renowned for several therapeutic folklore uses, in many Caribbean communities where as revealed in literature the leaves, bark and roots are made into tea for calming effects as sedative, heart tonic and hypertensive medication. In Nigeria, these potential health benefits are untapped since A. muricata is classified as an under-utilized plant. The present study determined the antidepressant and behavioral properties of the Nigerian grown Annona muricata in Sprague-Dawley rats using the open field test and forced swim test. Methods: Rats were administered A. muricata leaf extract (50, 150 and 300mg/kg) alone, as well as in combination with imipramine or sertraline (10mg/kg) for 14days. Results: The extract was found to reduce the explorative tendencies of the rats in the open field test. In the forced swim test the extract caused a significant reduction in immobility time and increased swimming time. Combination of the extracts with imipramine or sertraline further decreased the explorative tendencies at 150mg/kg concentration and the immobility time at 150 and 300mg/kg. Conclusion: The results obtained proposed a sedative and antidepressant-like effect of ethanol extract of A. muricata, confirming the ethnomedicinal use of the ethanol leaf extract of A. muricata for the management of depression.

Coadministration of ketamine with conventional antidepressants in animal models of depression

Background: Mental health has become one of the thrust areas for research given the complexity of the human mind and paucity of treatment strategies to handle its dysfunction effectively. The mental disorders gain prominence due to the damage they can cause to the individual themselves, the people who are in contact with them and to the society at large. Depression is a mental disorder which is encountered frequently and needs immediate attention. Conventional antidepressants such as selective serotonin reuptake inhibitor and tricyclic antidepressants are used in the management of depression. These drugs have a poor safety profile, take time for therapeutic response and have issues with patient compliance as a concern. Hence, it is postulated that concurrent administration of ketamine with conventional antidepressants would relieve the effects of depression more rapidly, would lower the dose of the later and would be more efficacious. Aims and Objectives: To study the antidepressant effect of coadministration of ketamine with conventional antidepressants in animal models of depression. Materials and Methods: The study was a randomized controlled animal study done on 36 male albino BALB/c mice divided into six groups, namely, Group A distilled water i.p., Group B imipramine 10 mg/kg (i.p.), Group C ketamine 10 mg/kg, Group D escitalopram 5 mg/kg (i.p.), Group E imipramine 10 mg/kg (i.p.) and ketamine 10 mg/kg (i.p.), and Group F escitalopram 5 mg/kg (i.p.) and ketamine 10 mg/kg (i.p.), respectively. The animal model used was the forced swim test. The reduction in immobility time was taken as the guide for the antidepressant effect. Results: The data were analyzed with the one-way ANOVA test using SPSS version 18. The results showed a significant reduction in immobility time and a statistical significance between the groups (P = 0.017). A post-hoc test showed that all the groups, i.e., B, C, D, E, and F significantly reduced the immobility time in comparison with the control Group A. Conclusion: The above results support the fact that coadministration of ketamine can be a treatment modality for the management of depression with the advantage of quicker onset of action.